Li Yongxin
Guangzhou Key Laboratory of Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
Front Psychiatry. 2024 Sep 19;15:1414295. doi: 10.3389/fpsyt.2024.1414295. eCollection 2024.
Depression is a prevalent mental disorder characterized by persistent negative mood and loss of pleasure. Although there are various treatment modalities available for depression, the rates of response and remission remain low. Xiaoyaosan (XYS), a traditional Chinese herbal formula with a long history of use in treating depression, has shown promising effects. However, the underlying mechanism of its therapeutic action remains elusive. The aim of this study is to investigate the neuroimaging changes in the brain associated with the antidepressant-like effects of XYS.
Here, we combined voxel-based morphometry of T2-weighted images and voxel-based analysis on diffusion tensor images to evaluate alterations in brain morphometry and microstructure between chronic social defeat stress (CSDS) model mice and control mice. Additionally, we examined the effect of XYS treatment on structural disruptions in the brains of XYS-treated mice. Furthermore, we explored the therapeutic effect of 18β-glycyrrhetinic acid (18β-GA), which was identified as the primary compound present in the brain following administration of XYS. Significant differences in brain structure were utilized as classification features for distinguishing mice with depression model form the controls using a machine learning method.
Significant changes in brain volume and diffusion metrics were observed in the CSDS model mice, primarily concentrated in the nucleus accumbens (ACB), primary somatosensory area (SSP), thalamus (TH), hypothalamus (HY), basomedical amygdala nucleus (BMA), caudoputamen (CP), and retrosplenial area (RSP). However, both XYS and 18β-GA treatment prevented disruptions in brain volume and diffusion metrics in certain regions, including bilateral HY, right SSP, right ACB, bilateral CP, and left TH. The classification models based on each type of neuroimaging feature achieved high accuracy levels (gray matter volume: 76.39%, AUC=0.83; white matter volume: 76.39%, AUC=0.92; fractional anisotropy: 82.64%, AUC=0.9; radial diffusivity: 76.39%, AUC=0.82). Among these machine learning analyses, the right ACB, right HY, and right CP were identified as the most important brain regions for classification purposes.
These findings suggested that XYS can prevent abnormal changes in brain volume and microstructure within TH, SSP, ACB, and CP to exert prophylactic antidepressant-like effects in CSDS model mice. The neuroimaging features within these regions demonstrate excellent performance for classifying CSDS model mice from controls while providing valuable insights into the antidepressant effects of XYS.
抑郁症是一种常见的精神障碍，其特征为持续的负面情绪和愉悦感丧失。尽管有多种治疗抑郁症的方法，但缓解率和治愈率仍然较低。逍遥散（XYS）是一种有着悠久治疗抑郁症历史的传统中药配方，已显示出有前景的疗效。然而，其治疗作用的潜在机制仍不清楚。本研究的目的是调查与逍遥散抗抑郁样作用相关的大脑神经影像学变化。
在此，我们结合基于体素的T2加权图像形态测量和基于体素的扩散张量图像分析，以评估慢性社会挫败应激（CSDS）模型小鼠和对照小鼠之间脑形态和微观结构的改变。此外，我们检查了逍遥散治疗对逍遥散处理小鼠大脑结构破坏的影响。此外，我们探索了18β-甘草次酸（18β-GA）的治疗效果，其被确定为逍遥散给药后大脑中存在的主要化合物。大脑结构的显著差异被用作使用机器学习方法区分抑郁症模型小鼠和对照小鼠的分类特征。
在CSDS模型小鼠中观察到脑容量和扩散指标的显著变化，主要集中在伏隔核（ACB）、初级体感区（SSP）、丘脑（TH）、下丘脑（HY）、基底内侧杏仁核（BMA）、尾壳核（CP）和压后皮质区（RSP）。然而，逍遥散和18β-GA治疗均预防了某些区域的脑容量和扩散指标破坏，包括双侧下丘脑、右侧初级体感区、右侧伏隔核、双侧尾壳核和左侧丘脑。基于每种神经影像学特征的分类模型都达到了较高的准确率水平（灰质体积：76.39%，AUC = 0.83；白质体积：76.39%，AUC = 0.92；各向异性分数：82.64%，AUC = 0.9；径向扩散率：76.39%，AUC = 0.82）。在这些机器学习分析中，右侧伏隔核、右侧下丘脑和右侧尾壳核被确定为用于分类目的的最重要脑区。
这些发现表明，逍遥散可以预防丘脑、初级体感区、伏隔核和尾壳核内脑容量和微观结构的异常变化，从而在CSDS模型小鼠中发挥预防性抗抑郁样作用。这些区域内的神经影像学特征在区分CSDS模型小鼠和对照小鼠方面表现出色，同时为逍遥散的抗抑郁作用提供了有价值的见解。
